Novel thermosensitive chitosan hydrogels: In vivo evaluation

Abstract Chitosan is an attractive biopolymer for the preparation of hydrogels. Its unique combination of biocompatibility, biodegradability, bioadhesivity, and tissue‐promoting abilities allows pharmaceutical applications. We investigated novel thermosensitive hydrogels based on chitosan homogeneously reacetylated to a deacetylation degree of about 50%, combined with selected polyols or polyoses such as trehalose, a nontoxic polysaccharide. The latter, a gel‐inducing and lyoprotective agent enabled the formulation to be lyophilized and rehydrated without affecting the thermosensitive behavior. This made possible long‐term storage and promoted its use in a clinical setup. The thermally induced sol‐gel transition allowed injectability and in situ setting. Rheological characterization revealed that storage moduli could be increased by one decade by increasing the chitosan concentration from 1.4 to 2.2% (w/w). Evaluation in vivo provided evidence of in situ implant formation in subcutaneous tissue of Sprague–Dawley rats and permanence for up to 3 months. Histopathological analysis demonstrated a mild, chronic, inflammatory reaction that disappeared with the complete absorption of the gel implant over a few months period. Such in situ forming hydrogels could be advantageous for specific applications in drug delivery and tissue engineering. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009